Disconnection of bonds

Because of the symmetry of TM 329 there are only two different disconnections of bonds between two common atoms. 

Analysis Marking the common atoms we find there are three possible disconnections of bonds between them, but only a or c give us simpler precursors. Both also are logical in that we can immediately write reagents for the synthons. 

HP-4 EGA, in order to functionalise or create new consonant bifunctional relationships (new dissonances must be avoided) sometimes, introduce a double bond prior to disconnection of bonds (conjugated if a C=0 group is already present). 

Although the disconnection of the "strategic bonds" should be in principle the solution of choice in designing a rational synthesis of twistane (see below, 13.1.2), syntheses based in the disconnection of bonds other than those have also been... 

In contrast to Nicolaou s synthetic plan, the retrosynthetic analysis of Holton s approach preserves the non-synthetically significant B ring and proceeds through disconnection of bonds which are involved in the D and C rings, to arrive finally to the bicyclo[5.3.1]undecane derivative 32, as the starting material. 

SAMPLE SOLUTION (a) Because 2-hexanol is a secondary alcohol, we consider the reaction of a Grignard reagent with an aldehyde. Disconnection of bonds to the hydroxyl-bearing carbon generates two pairs of structural fragments ... 

We now leave disconnections of bonds between carbon and other atoms (C-X disconnections) and turn to the more challenging C-C disconnections. These are more challenging because organic compounds contain many C-C bonds and it is not clear at first which ones should be disconnected. There is some very good news the synthons that we met in chapter 6 for two-group C-X disconnections are the ones we shall use for one-group C-C disconnections. We start with an introduction to the three main types. In each case we shall replace one of the heteroatoms by a carbon unit R . 

The first strategy you should try out when faced with the synthesis of an aromatic heterocyclic ring is the disconnection of bonds between the heteroatom or atoms and carbon, with the idea of using the heteroatoms as nucleophiles and the carbon fragment as a double electrophile. 

To show how this is done in practice, we will examine Nicolaou s synthesis of zoopatenol 212, a biologically active natural diterpenoid (Scheme 2.91). A retrosynthetic analysis of this structure envisions the disconnection of bonds a, b, and c, to lead to rather simple precursors, the bromo ketone 213 and the triol 214. A formal pathway for the assemblage of 212 from these precursors involves several steps, as outlined in Scheme 2.91. This plan appears strategically... 

The structure of cij-4-tert-butylcyclohexanecarboxylic acid 236 (Scheme 2.99) seems to be rather simple for retrosynthetic analysis. The most obvious options in this analysis involve the disconnection of bonds a or b as shown. 

Below are summarized some important guidelines for choosing disconnections of bonds. Thus, the initial stage of the retrosynthetic analysis key fragments are recognized, which then can be recombined in the forward synthetic step in an efficient way. ... 

Disconnections of bonds should be carried out only if the resultant fragments can be reconnected by known and reliable reactions. 

Disconnection of bond (a) in (46) would separate the molecule into two simple starting materials and fortunately (46) is a 1,5-diketone with a reverse Michael disconnection (Chapter 21) just where we want it. 

A logical extension of this strategy, particularly important for bridged polycyclic compounds, is the common atom approach. Atoms common to two or more rings (the common atoms) are marked disconnections of bonds to these atoms must inevitably reduce the number of rings. 

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